Gene mutation patterns of Chinese acute myeloid leukemia patients by targeted next-generation sequencing and bioinformatic analysis
Gene mutation patterns of Chinese acute myeloid leukemia patients by targeted next-generation sequencing and bioinformatic analysis
复制标题
通过靶向二代测序和生物信息学分析中国急性髓系白血病患者的基因突变模式
DOI：
10.1016/j.cca.2018.01.006
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发表时间：
2018-04-01
影响因子：
5
通讯作者：
Ma, Daoxin
中科院分区：
文献类型：
--
作者：
Han, Xiaoyu;Li, Wei;Ma, Daoxin
目的：传统的基于细胞遗传学的急性髓系白血病（AML）危险分层不能满足准确预后评估的需求。近年来，基因突变被发现是更准确的危险分层的潜在标志物，但关于中国AML突变筛查的报道有限。方法：提取78例中国AML患者的骨髓基因组DNA，采用下一代测序技术（NGS）进行靶基因突变谱分析。采用统计学和生物信息学方法分析基因突变与临床特征之间的相关性，并将我们的结果与癌症基因组图谱研究网络（TCGA）公开的AML数据集进行比较。我们发现FLT 3和TET 2基因突变患者的骨髓原始细胞、外周血原始细胞和白色血细胞（WBC）计数较高，SRSF 2基因突变与年龄有关，FLT 3-ITD、DNMT 3A、IDH 1、TET 2和SRSF 2基因突变是影响总生存率的危险因素。此外，我们还发现了15个新的突变，并在6个基因上发现了中国人和高加索人AML的突变发生率差异。生物信息学分析显示基因突变与表达及药物敏感性之间存在一定的关系。结论：应用NGS技术研究了中国AML患者的基因突变模式，揭示了基因突变与临床特征的相关性。因此，我们建议常规检测可疑基因，以更好地预测预后和个体化治疗。
Purposes: The conventional risk stratification of acute myeloid leukemia (AML), based on cytogenetics, cannot meet the demand for accurate prognostic evaluations. In recent years, gene mutations are found to be potential markers for more accurate risk stratification, but reports on mutation screening of Chinese AML are limited. We aim to display the mutation patterns of Chinese AML patients, reveal the genotype-phenotype correlations and make a comparison with Caucasians patients.Methods: Genome DNA from 78 patients' bone marrow were extracted for targeted gene mutation panel by next generation sequencing (NGS) technology. Statistics and bioinformatics were used to analyze the correlations between gene mutations and clinical features, as well as the comparison of our results with the Cancer Genome Atlas Research Network (TCGA) public AML dataset.Results: We found patients with mutations of FLT3 and TET2 had higher bone marrow blasts, peripheral blasts and white blood cell (WBC) count, mutations of SRSF2 were related with age, and mutations of FLT3-ITD, DNMT3A, IDH1, TET2 and SRSF2 were risk factors for overall survival. What's more, we discovered 15 novel mutations and difference of mutational incidence in 6 genes between Chinese and Caucasians AML. Bioinformatic analysis revealed some relationship between gene mutations and expressions as well as drug sensitivities.Conclusions: We made an investigation on the mutation patterns of Chinese AML patients by NGS technique and revealed correlations between gene mutations and clinical features. Thus we recommend routine testing of suspected genes for better prognostic prediction and individualized treatment.